3D bioprinted endothelial cell-microglia coculture for diabetic retinopathy modeling.

Diabetic retinopathy (DR) is a common diabetes complication leading to vision impairment or blindness due to retinal vasculature alterations. Hyperglycemia induces structural alterations, inflammation, and angiogenic factor upregulation. Current treatments targeting vascular endothelial growth factor are insufficient for approximately 20% of DR patients, necessitating alternative approaches. Microglia (MG), essential for retinal homeostasis, remains underexplored in DR. This study used digital light processing bioprinting to construct a 3D coculture model of endothelial cells (ECs) and MG under varying glucose conditions, with a hydrogel stiffness of 4.6-7.1 kPa to mimic the extracellular matrix property of retina plexiform. Our results showed that high glucose levels influenced both EC and microglial phenotypes, gene expression, and angiogenic potential. Increasing glucose from 5 mM to 25 mM reduces drug efficacy by 17% for Aflibercept in EC monoculture, and 25% and 30% for Aflibercept and Conbercept in EC-MG coculture, respectively, suggesting that diabetic condition and MG presence could interfere with drug responses. In conclusion, our findings emphasize the importance of cellular interactions and microenvironmental factors in DR therapy, aiming to identify novel strategies and improve understanding of MG's role in disease pathogenesis.

BTG2 suppresses the growth and metastasis of cervical squamous cell carcinoma.

BACKGROUND: Cervical cancer is the fourth most common malignancy in women, of which cervical squamous cell carcinoma (CESC) is the main pathological type of cervical cancer. B-cell translocation gene 2 (BTG2) protein has been recognized as a tumor suppressor in several cancer types. However, BTG2 expression and molecular function in CESC are unknown. METHODS: In this study, we first assessed the expression of BTG2 in tumor tissue specimens from CESC patients using immunohistochemical staining and real-time quantitative PCR, and explored the relationship between BTG2 expression status and clinical manifestations. Next, we constructed BTG2 knockdown and overexpression CESC cell lines to observe the effects of BTG2 on CESC proliferation and metastasis at the cellular level. Finally, we employed a nude mouse xenograft tumor model in an in vivo experiment to observe the effect of BTG2 on tumorigenesis in vivo. RESULTS: The results showed that the expression of BTG2 protein was lower in CESC tissues than in normal tissues, and high BTG2 expression was associated with better survival in CESC patients versus CESC patients. The results of cellular assays confirm that overexpression of BTG2 inhibits the proliferation, migration and metastasis of CESC cells. Nude mouse xenograft tumor model showed that overexpression of BTG2 inhibited tumor growth in vivo, and conversely knockdown of BTG2 promoted tumor growth. CONCLUSION: In summary, our data suggest that BTG2 acts as a tumor suppressor in CESC and inhibits the growth and metastasis of CESC. BTG2 may serve as a potential prognostic marker in CESC and is expected to provide a therapeutic strategy for patients with CESC.

Physicochemical and functional properties of the protein-starch interaction in Chinese yam.

Protein-starch interaction has an important impact on the properties of starchy foods rich in protein, but the contribution of the interaction to Chinese yam still remains unclear. This study aimed to characterize the physicochemical and functional properties related to the possible interaction between starch and protein in Chinese yam. Differential scanning calorimetry and rapid viscosity analyzer results revealed that the gelatinization temperature increased in protein and starch cross-linked powder, while the peak viscosity and the setback viscosity decreased. The swelling power and solubility at 80°C and 95°C decreased with increasing protein ratio in the powder. In vitro starch digestibility test indicated that a high protein ratio could rapidly reduce digestible starch, but increase both slowly digestible starch and resistant starch. Protein could act as the physical barrier toward starch against heating and digestion to exert the influence on starch properties. Fourier transform infrared spectroscopy test revealed the interaction between protein and starch. These results revealed the role of protein-starch interaction and provided beneficial information for the utilization of Chinese yam.

More Than Just Static: Dynamic Functional Connectivity Changes of the Thalamic Nuclei to Cortex in Parkinson's Disease With Freezing of Gait.

Background: The thalamus is not only a key relay node of the thalamocortical circuit but also a hub in the regulation of gait. Previous studies of resting-state functional magnetic resonance imaging (fMRI) have shown static functional connectivity (FC) between the thalamus and the cortex are disrupted in Parkinson's disease (PD) patients with freezing of gait (FOG). However, temporal dynamic FC between the thalamus and the cortex has not yet been characterized in these patients. Methods: Fifty PD patients, including 25 PD patients with FOG (PD-FOG) and 25 PD patients without FOG (PD-NFOG), and 25 healthy controls (HC) underwent resting-state fMRI. Seed-voxel-wise static and dynamic FC were calculated between each thalamic nuclei and other voxels across the brain using the 14 thalamic nuclei in both hemispheres as regions of interest. Associations between altered thalamic FC based on significant inter-group differences and severity of FOG symptoms were also examined in PD-FOG. Results: Both PD-FOG and PD-NFOG showed lower static FC between the right lateral posterior thalamic nuclei and right inferior parietal lobule (IPL) compared with HC. Altered FC dynamics between the thalamic nuclei and several cortical areas were identified in PD-FOG, as shown by temporal dynamic FC analyses. Specifically, relative to PD-NFOG or HC, PD-FOG showed greater fluctuations in FC between the left intralaminar (IL) nuclei and right IPL and between the left medial geniculate and left postcentral gyrus. Furthermore, the dynamics of FC between the left pulvinar anterior nuclei and left inferior frontal gyrus were upregulated in both PD-FOG and PD-NFOG. The dynamics of FC between the right ventral lateral nuclei and left paracentral lobule were elevated in PD-NFOG but were maintained in PD-FOG and HC. The quantitative variability of FC between the left IL nuclei and right IPL was positively correlated with the clinical scales scores in PD-FOG. Conclusions: Dynamic FC between the thalamic nuclei and relevant associative cortical areas involved in sensorimotor integration or cognitive function was disrupted in PD-FOG, which was reflected by greater temporal fluctuations. Abnormal dynamic FC between the left IL nuclei of the thalamus and right IPL was related to the severity of FOG.

Physicochemical and structural properties of low-amylose Chinese yam (Dioscorea opposita Thunb.) starches.

Nuoshanyao (NSY), Tiegunshanyao (TSY) and Huaishanyao (HSY) are the main cultivars of Chinese yam (Dioscorea opposita Thunb.) widely grown in China. The composition, physicochemical properties, morphology, and thermal properties of the starches from these cultivars were investigated in this study. NSY starch (17.0%) was much lower in amylose content than other cultivars (33.4-34.5%). The average particle diameter of the starches ranged from 25.83 to 28.93 µm. Weight-average molecular weights (Mw) and number-average molecular weights (Mn) ranged from 1.29 to 1.84 × 105 g/mol and 5.93 to 8.36 × 104 g/mol, respectively. NSY starch had higher gelatinization temperature (71.5 °C), enthalpy (14.14 J/g), peak viscosity (8590 cP) and swelling power (12.0%) than TSY and HSY. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) tests indicated that Chinese yam starches had CB-type crystalline structure with crystallinity ranging from 21.91% to 27.08% and a short-range ordered structure. To, Tp, ΔH, peak viscosity and swelling power at 95 °C were significantly correlated to amylose content. The low-amylose NSY starch was found to have high gelatinization temperature, enthalpy, peak viscosity and swelling power. These specific physicochemical and structural properties indicated the industrial potential of low-amylose yam starch.

Molecular Assembly of a Durable HRP-AuNPs/PEDOT:BSA/Pt Biosensor with Detailed Characterizations.

In this study, we provided the detailed characterizations of our recent HRP-AuNPs/PEDOT:BSA/Pt biosensor, constructed through a simple fabrication procedure with improved stability and good sensitivity. Raman and Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy not only confirmed the synthesis of conductive PEDOT where BSA was the template for the polymerization, but also provided further insights into the stable immobilization of AuNP on the PEDOT:BSA film. Scanning electron microscopy revealed that the attachment of AuNPs were stable under a high salt environment. The current technology demonstrates a feasible procedure to form a functional AuNPs/PEDOT:BSA film that has potential applications in the fabrication of various biosensors and electric devices.

Relationship between cerebellar structure and emotional memory in depression.

BACKGROUND: A few studies have been conducted on the relationship between cerebellar volume and emotional memory or clinical severity in major depressive disorder (MDD). In this study, we aimed to compare the volume and density of the cerebellar gray matter (GM) in patients with MDD and in healthy controls (HCs) and explore the association between these cerebellar parameters and measurements of emotional memory and clinical severity. METHOD: Voxel-based morphometry (VBM) and Individual Brain Atlases using Statistical Parametric Mapping (IBASPM) were used to assess GM density and volume in the cerebellum, respectively, in patients with MDD and the HCs. Indicators of emotional memory performance were measured, including the hit rate (HR), rate of false alarm (FA), precision (Pr = HR - FA) and emotional memory enhancement [∆Pr = Pr(emotion) - Pr(neutral)] values. Beck Depression Inventory (BDI) scores were used to measure the severity of depression. RESULTS: In the patients with MDD, the GM density was decreased in three cerebellar cortical regions and increased in three cerebellar cortical regions (p < .005). The GM volumes in eight cerebellar cortical regions were significantly smaller in the patients with MDD than in the HC subjects (p < .05). In the patients with MDD, the GM volume was correlated with the ∆Pr (p < .05) in two cerebellar cortical regions. The BDI scores were significantly correlated with the relative GM densities (p < .05) in 5 cerebellar cortical regions, and the GM volumes in 13 cerebellar cortical regions were correlated with the BDI scores in patients with MDD. CONCLUSIONS: Emotional memory and the severity of depressive symptoms are associated with structural changes in both the posterior and anterior GM regions in the cerebellum in patients with MDD. These findings could be useful for improving our understanding of the neurobiological mechanisms underlying emotional memory and explaining the abnormalities of the neural correlates that are associated with MDD.

Azo dye decolorization by a halotolerant exoelectrogenic decolorizer isolated from marine sediment.

Based on both capabilities of extracellular electron transfer and high salt tolerance, marine exoelectrogenic bacteria have the potential to serve as halotolerant/halophilic exoelectrogenic decolorizers (HEDs) for textile wastewater treatment. However, research in this area is still rare. In this study, we employed Shewanella marisflavi EP1 for this purpose. The results showed that EP1 could decolorize Xylidine Ponceau 2R (XP2R) under high NaCl concentrations up to 20%. Two different mechanisms were involved: degradation and bioflocculation. XP2R was decolorized by degradation in the range of 0-7.4% NaCl, by bioaugmented flocculation in 10-20% NaCl; and the range of 7.4-10% NaCl was the transition period from degradation to flocculation. Considering the property of flocculation by strain EP1, it is reasonable that XP2R was hard to penetrate into EP1 cells, thus it was an extracellular process of decolorization. The overall results further suggested that like EP1, marine exoelectrogenic bacteria might serve as a category of functional microbes (i.e., HEDs) for textile wastewater treatment.

A Novel Conductive Poly(3,4-ethylenedioxythiophene)-BSA Film for the Construction of a Durable HRP Biosensor Modified with NanoAu Particles.

In this study, we have investigated the contribution of bovine serum albumin (BSA) to the durability of the electrochemically synthesized poly(3,4-ethylenedioxythiophene) (PEDOT) film on a platinum (Pt) electrode. The electrode was capable to effectively adsorb the nano Au particles (AuNPs) to form a uniform layout, which was then able to immobilize the horseradish peroxidase (HRP) to construct a functional HRP/AuNPs/PEDOT(BSA)/Pt biosensor. Cyclic voltammetry was employed to evaluate the performance of the biosensor through the measurement of hydrogen peroxide. Our results revealed a satisfied linear correlation between the cathodic current and the concentration of H2O2. Furthermore, the addition of oxidized form of nicotinamide adenine dinucleotide, or NAD⁺, as the electron transfer mediator in the detection solution could dramatically enhance the sensitivity of detection by about 35.5%. The main advantages of the current biosensor are its durability, sensitivity, reliability, and biocompatibility.

Identification of Cortex Eucommiae from different producing areas by FTIR microspectroscopy.

In this paper, FTIR microspectroscopy was used to compare Cortex Eucommiae from Anhui Province (A), Henan Province (B) and Sichuan Province (C) of China. High-resolution spectra were obtained with good reproducibility. From IR spectra, some obvious differences in band frequency could be observed among Cortex Eucommiae A-C. Curve fitting result indicated that polysaccharides' structures and contents were different among Cortex Eucommiae A-C. To distinguish Cortex Eucommiae from different producing areas, the A1245/A1328 ratio might be an exceptionally practical factor. Additionally, FTIR microspectroscopy could identify Cortex Eucommiae A-C with 89.5% accuracy in combination with hierarchical cluster analysis. The results suggest FTIR microspectroscopy is very easy and efficient for distinguishing Cortex Eucommiae from different areas, and also indicate FTIR microspectroscopy may be practical for TCM research.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 µM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.

Rapid decolorization of methyl orange by a novel Aeromonas sp. strain DH-6.

Azo dyes are extensively used, but are recalcitrant and refractory. In this study, an indigenous strain DH-6 was isolated and identified as Aeromonas sp. based on 16S rDNA analysis for its excellent methyl orange (MO) decolorizing capability. Plackett-Burman design and response surface methodology (RSM) were employed to investigate the effect of operational parameters on decolorization and to optimize the decolorization process. Based on the results the concentrations of glucose, Na2HPO4 and MO and temperature were selected as the four significant parameters of RSM. The optimal conditions for MO decolorization by the strain were as follows: 3.0 g/L glucose, 4.9 g/L Na2HPO4, 100 mg/L MO, and at 40 °C. The verification tests showed that 95.5% decolorization was observed after incubation for 2 h, which is within the confidence interval. Under the optimal conditions, the kinetics of the decolorization fitted the first-order model well (R(2) = 0.969). As the strain DH-6 still showed a good decolorizing capability at a relatively high temperature, it is considered a candidate for azo dye bioremediation in some tropical or subtropical regions.

Reduced serum levels of triglyceride, very low density lipoprotein cholesterol and apolipoprotein B in Parkinson's disease patients.

BACKGROUND: Previous studies have shown a lower incidence of stroke in Parkinson's disease (PD) patients. The role of the lipids and lipoproteins as risk factors for stroke is uncertain in the lower prevalence of stroke in PD patients. OBJECTIVES: To explore the lipids and lipoproteins serum levels in PD patients. METHODS: A retrospective study was performed on 110 PD patients (PD group), 130 controls with non-cerebrovascular neurological diseases (OD group), 140 acute intracerebral hemorrhage patients (ICH group) and 140 acute cerebral infarction patients (CI group). The records about serum levels of lipids and lipoproteins were analyzed. RESULTS: There were significant differences for the serum level of triglyceride (F = 5.031, p=0.002), very low density lipoprotein cholesterol (F = 5.313, p=0.001), apolipoprotein B (F = 16.038, p<0.0001) in the four groups. PD group had a significantly lower serum level of triglyceride (TG) than the OD (p=0.032), ICH (p=0.00047) and CI (p=0.001) groups. Very low density lipoprotein cholesterol (VLDL-C) serum level was significantly lower in PD group than in OD (p=0.039), ICH (p=0.00021) and CI (p=0.001) groups. There was a significantly lower serum level of apolipoprotein B (apo B) in PD group than in OD (p=0.002), ICH (p<0.0001) and CI (p<0.0001) groups. CONCLUSIONS: There are reduced serum levels of TG, VLDL-C and apo B in PD patients, which may be related to the decreased prevalence of stroke in PD patients.

Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

Cerebrospinal fluid high-mobility group box protein 1 in neuromyelitis optica and multiple sclerosis.

BACKGROUND: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are two autoimmune inflammatory demyelinating diseases in the central nervous system. Interleukin (IL)-6 and IL-17 may play important roles in the pathogenesis of these diseases. High-mobility group box protein 1 (HMGB1) can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17. However, whether cerebrospinal fluid (CSF) HMGB1 levels were altered in NMO and MS patients is still unclear. OBJECTIVES: It was our aim to measure the CSF HMGB1 concentration in NMO patients and explore their relationship with IL-6, IL-17 and disease activity. METHODS: CSF HMGB1 was measured by enzyme-linked immunosorbent assay in NMO (n = 22) and MS (n = 18) patients as well as in controls (n = 14). RESULTS: CSF HMGB1 was notably higher in the NMO group compared with controls (p = 0.007). CSF HMGB1 positively correlated with IL-6 and IL-17 in NMO patients (IL-6, p = 0.034; IL-17, p < 0.001). CONCLUSIONS: In conclusion, our study suggests that CSF levels of HMGB1 are increased in patients with NMO and reflect the neuroinflammatory process.

Increased plasma interleukin-32 expression in patients with neuromyelitis optica.

PURPOSE: Neuromyelitis optica (NMO) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The pathogenesis of NMO remains unclear. IL-32 is emerging as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory diseases. Whether IL-32 levels are elevated in NMO patients is unclear. We aimed to determine whether IL-32 levels are elevated in NMO patients and explore its relationship with IL-6, IL-17, and Expanded Disability Status Scale (EDSS) scores. METHODS: Plasma IL-32α, IL-6 and IL-17A were measured by enzyme-linked immunosorbent assay in NMO (n = 26), MS (n = 23) and 22 healthy controls. RESULTS: We found IL-32α levels were higher in NMO patients compared with MS (p = 0.020) and healthy controls (p = 0.00001). IL-32α levels were increased in MS patients compared with controls (p = 0.009). IL-32α positively correlated with IL-6 and IL-17A levels and EDSS scores in NMO patients. CONCLUSIONS: In summary, plasma IL-32α levels are associated with inflammatory responses in NMO patients.

Viral infection of tobacco plants improves performance of Bemisia tabaci but more so for an invasive than for an indigenous biotype of the whitefly.

The ecological effects of plant-virus-vector interactions on invasion of alien plant viral vectors have been rarely investigated. We examined the transmission of Tomato yellow leaf curl China virus (TYLCCNV) by the invasive Q biotype and the indigenous ZHJ2 biotype of the whitefly Bemisia tabaci, a plant viral vector, as well as the influence of TYLCCNV-infection of plants on the performance of the two whitefly biotypes. Both whitefly biotypes were able to acquire viruses from infected plants and retained them in their bodies, but were unable to transmit them to either tobacco or tomato plants. However, when the Q biotype fed on tobacco plants infected with TYLCCNV, its fecundity and longevity were increased by 7- and 1-fold, respectively, compared to those of the Q biotype fed on uninfected tobacco plants. When the ZHJ2 biotype fed on virus-infected plants, its fecundity and longevity were increased by only 2- and 0.5-fold, respectively. These data show that the Q biotype acquired higher beneficial effects from TYLCCNV-infection of tobacco plants than the ZHJ2 biotype. Thus, the Q biotype whitefly may have advantages in its invasion and displacement of the indigenous ZHJ2 biotype.